RESUMO
Background: In the end stage of malignant bone and soft tissue tumors with lung metastasis, it is often necessary to relieve symptoms of dyspnea due to tumor enlargement and carcinomatous lymphangitis. We report a case in which nasal continuous positive airway pressure (nasal CPAP) was effective as a palliative treatment. Case: A 66-year-old male underwent wide resection with a diagnosis soft tissue sarcoma of right femur. Four years after surgery, he was hospitalized for hilar lymph node metastasis, multiple bone metastases, and carcinomatous lymphangitis. He was treated with nasal CPAP for dyspnea, and communication was possible until the day before his death. Discussion: For end-stage respiratory symptoms, medication therapy such as morphine or steroids is often used for palliation, but often symptoms are not sufficiently improved. Nasal CPAP might be a useful treatment for palliation for rapidly progressing respiratory failure.
RESUMO
The TLR7 and TLR9 signalings are implicated in the regulation of the immune system through type-I interferon induction. Preclinical studies have demonstrated the immunomodulatory and antitumor effects of TLR7 and TLR9 agonists in combination with cetuximab. We tested the hypothesis that genetic variations in TLR7 and TLR9 and their downstream molecules IRF5 and IRF7 were associated with outcomes in metastatic colorectal cancer (mCRC) patients receiving cetuximab-based chemotherapy. Six single nucleotide polymorphisms (SNPs) in TLR7, TLR9, IRF5 and IRF7 were tested for the association with RR, PFS, and OS in KRAS-wild type mCRC patients. Patients treated with FOLFIRI + cetuximab or FOLFIRI + bevacizumab in the FIRE-3 trial served as a discovery set (FIRE3-Cet, n = 244) or a control set (FIRE3-Bev, n = 246), respectively. Patients treated with FOLFOX or SOX + cetuximab in the JACCRO-CC05/06 trial served as a validation set (JACCRO, n = 76). Genomic DNA isolated from tumor tissue samples was analyzed by PCR-based direct sequencing. In the discovery cohort, patients with the TLR7 rs3853839 G/G variant showed a trend toward longer PFS than those with any C variants (median 10.0 vs. 11.8 months, HR 1.39, p = 0.092). This preliminary association was confirmed in the validation cohort, and those with the G/G genotype showed a PFS benefit compared with others (univariate: 9.1 vs. 11.6 months, HR 2.04, p = 0.005, multivariate: HR 2.02, 95% CI: 1.14-3.55, p = 0.015). This association was not observed in the control cohort. Our findings suggest that TLR7 rs3853839 predicts the outcome of cetuximab-based chemotherapy in mCRC patients.
